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Epithelial ovarian cancer (EOC) has the highest mortality rate in western countries among gynecological cancers. It is often diagnosed at the stage of peritoneal carcinomatosis. Therapeutic management is based on macroscopic complete cytoreductive surgery (MCCS) and on chemotherapy. One hypothesis explaining the high rate of peritoneal recurrence is the existence of microscopic peritoneal involvement not resected during surgery. The objective of this study is to search for microscopic peritoneal metastases (MPm) in macroscopically healthy peritoneum (MHP) after MCCS for EOC. The secondary objective is to find out whether the MPm express the isoform α of the folate receptor (FRα), a therapeutic target for targeted therapies. This is a descriptive, prospective monocentric cohort study. MHP biopsies are taken at the end of CCMC for CEO. A search for the expression of FRα by immunohistochemistry is carried out on MPm, macroscopic peritoneal metastases and biopsies performed before neoadjuvant chemotherapy. Thirty patients were included, between January the 1st, 2018 and June the 1st, 2019. MPM were identified in 7 patients (23%). 75% of MPm overexpress FRα. A mathematical approach allows us to estimate that the probability of residual microscopic metastases after surgery is close to 100%. Patients with EOC have unresected MPm at MCCS. The presence of MPm is an argument for the development of complementary intracavitary treatments. The overexpression of FRα makes it possible to envisage targeted therapies.; Le cancer épithélial de l’ovaire (CEO) est le cancer gynécologique dont le taux de mortalité est le plus élevé dans les pays occidentaux. Il est souvent diagnostiqué au stade de carcinose péritonéale. La prise en charge thérapeutique repose sur une chirurgie de cytoréduction macroscopiquement complète (CCMC) et sur une chimiothérapie. Une hypothèse expliquant le taux élevé de récidive péritonéale est l’existence d’une atteinte péritonéale microscopique non réséquée lors de la chirurgie. L’objectif de cette étude est de rechercher des métastases péritonéales microscopiques (MPm) en péritoine macroscopiquement sain (PMS) après CCMC pour CEO. L’objectif secondaire est de rechercher si les MPm expriment l’isoforme α du récepteur au folate (FRα), cible thérapeutique pour des thérapies ciblées. Il s’agit d’une étude de cohorte descriptive, monocentrique prospective. Les biopsies péritonéales en PMS sont prélevées en fin de CCMC pour CEO. Une recherche de l’expression de FRα par immunohistochimie est réalisée sur les MPm, les métastases péritonéales macroscopiques et les biopsies réalisées avant chimiothérapie néoadjuvante. Trente patientes ont été incluses, entre le 1er janvier 2018 et le 1er juin 2019. Des MPm ont été identifiées chez 7 patientes (23%). 75% des MPm surexpriment FRα. Une approche mathématique permet d’estimer que la probabilité d’une atteinte microscopique résiduelle à l’issue de la chirurgie est proche de 100%. Les patientes atteintes d’un CEO présentent des MPm non réséquées lors d’une CCMC. La présence des MPm est un argument pour le développement de traitements complémentaires intracavitaires. La surexpression de FRα permet d’envisager des thérapies ciblées.

Despite being associated with a very poor prognosis, long-term survivors across all series of Desmoplastic Small Round Cell Tumor (DSRCT) have been reported.To analyze patients 'characteristics associated with a prolonged survival after DSRCT diagnosis.All consecutive patients treated for DSRCT in nine French expert centers between 1991 and 2018 were retrospectively analyzed. Patients with a follow-up of less than 2 years were excluded and cure defined as being disease-free at least 5 years.100 pts were identified (median age 25 years, 89% male). 27 had distant metastases at diagnosis and 80 pts underwent upfront chemotherapy (CT). 71 pts were operated, 20 pts without prior CT). Surgery was macroscopically complete (CC0/1) in 50 pts. Hyperthermic intraperitoneal Chemotherapy (HIPEC) was administered during surgery in 15 pts 54 pts had postoperative CT and 26 pts had postoperative whole abdomino-pelvic RT (WAP-RT). After a median follow-up of 103 months (range 23-311), the median overall survival (OS) was 25 months. The 1- year, 3-year and 5-year OS rates were 90%, 35% and 4% respectively. 5 patients were considered cured after a median disease-free interval of 100 months (range 22-139). Predictive factors of cure were female sex (HR = 0.49, p = 0.014), median PCI12 (HR = 0.32, p = 0.0004), MD Anderson stage I (HR = 0.25, p 0.0001), CC0/1 (HR = 0.34, p 0.0001), and WAP-RT (HR = 0.36, p = 0.00013). HIPEC did not statistically improve survival.Cure in DSRCT is possible in 5% of patients and is best achieved combining systemic chemotherapy, complete cytoreductive surgery and WAP-RT. Despite aggressive treatment, recurrence is common and targeted therapies are urgently needed.

International audience

International audience; PURPOSE:Ovarian cancer is the most common deadly cancer of gynecologic origin. Patients often are diagnosed at advanced stage with peritoneal metastasis. There are many rare histologies of ovarian cancer; some have outcomes worse than serous ovarian cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be considered for patients with recurrence. This study was designed to assess the impact of CRS and HIPEC on survival of patient with peritoneal metastasis from rare ovarian malignancy.METHODS:A prospective, multicentric, international database was retrospectively searched to identify all patients with rare ovarian tumor (mucinous, clear cells, endometrioid, small cell hypercalcemic, and other) and peritoneal metastasis who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI) and BIG-RENAPE working group. The postoperative complications, long-term results, and principal prognostic factors were analyzed.RESULTS:The analysis included 210 patients with a median follow-up of 43.5 months. Median overall survival (OS) was 69.3 months, and the 5-year OS was 57.7%. For mucinous tumors, median OS and DFS were not reached at 5 years. For granulosa tumors, median overall survival was not reached at 5 years, and median DFS was 34.6 months. Teratoma or germinal tumor showed median overall survival and DFS that were not reached at 5 years. Differences in OS were not statistically significant between histologies (p = 0.383), whereas differences in DFS were (p

Introduction Peritoneal metastasis (PM) of hepatocellular carcinoma (HCC) without distant spread are rare. The related prognosis is poor without standard treatment available. The role of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly documented. Methods An international multicentric cohort was constituted by retrospective analysis of 21 patients undergoing CRS/HIPEC for PM of HCC between 1992 and 2016 from 10 reference centers of PSOGI. Data on clinical features, treatment strategies, and survival outcomes were analyzed. Results The median time interval from the diagnosis of PM to the procedure was 4.5 months. The median peritoneal cancer index was 14. Sixteen patients had complete cytoreduction (CCR0-1). Ten patients had grades 3 to 4 complications. The median duration of follow-up was 52.2 months. The median OS was 46.7 months. The projected 3y-OS and 5y-OS were 88.9 and 49.4% respectively. The median OS for patients with CCR0-1 resection was not reached whereas it was 5.9 months for those with CCR2-3 resection after CRS (p = 0.0005). The median RFS was 26.3 months and projected RFS at 3 years of 36.5 months Three prognostic factors were associated with improved RFS in the univariate analysis: preoperative chemotherapy (p = 0.0156), PCI >15 (p = 0.009), Number of chemotherapy agents used for HIPEC (p = 0.005). Conclusion CRS/HIPEC is a safe and effective approach in selected patients with PM of HCC. CRS/HIPEC gives the patient a chance for a good relapse free and overall survival and should be considered as an option.

Medullary thyroid carcinomas (MTCs) complicated by ectopic Cushing's syndrome (CS) have a poor prognosis, partially due to the difficulty in controlling hypercortisolism by adrenal blocking drugs. Recent reports (including the initial follow-up of this patient) have suggested that tyrosine kinase inhibitors (TKIs) may be a therapeutic option due to an anti-secretory action on ACTH. However, there is a lack of long-term follow-up studies.The case is reported of a 58-year-old man with MTC-related CS resistant to a combination of several anti-cortisolic drugs. Vandetanib, an oral multi-TKI that targets RET in particular, was initiated, and a rapid reversal of the hypercortisolism was observed without any change in tumor size. Vandetanib was briefly interrupted twice, once for 45 days because of side effects and a second time for 10 days to schedule surgical debulking. Each time, plasma cortisol and calcitonin levels increased after TKI withdrawal and were rapidly lowered by vandetanib reintroduction. As described in other cases of CS caused by MTC, a marked ACTH increase after desmopressin stimulation was observed before vandetanib therapy. In contrast, a blunted ACTH response to desmopressin was documented throughout the course of vandetanib treatment. This modulation of the tumoral ACTH production is a strong argument in favor of a TKI anti-secretory action. A left thyroid lobectomy and a modified neck dissection were performed one year after the initiation of vandetanib in order to reduce the tumor mass. An activating M918T RET (c.2753TC) somatic mutation was identified in a lymph node metastasis.Three years and eight months after vandetanib initiation, there was no sign of recurrence of hypercortisolism. This case illustrates the long-term effectiveness of vandetanib in maintaining the control of hypercortisolism in MTC-related CS.

International audience; OBJECTIVE:This study was designed to identify factors associated with morbidity and mortality in patients older than 70 years who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC).BACKGROUND:Major surgery is associated with higher morbidity and mortality in elderly patients. For PC, CRS and HIPEC is the only current potential curative therapy, but the risks inherent to this patient population have called its benefits into question.METHODS:We retrospectively analyzed a multi-center database from 1989 to 2015. All patients who underwent CRS and HIPEC for PC were selected and patients older than 70 years were matched 1:4 with a younger cohort according to cancer origin, peritoneal cancer index (PCI), and completeness of cytoreduction. Major morbidity and mortality were analyzed.RESULTS:Of 2328 patients, 188 patients older than aged 70 years were matched with 704 younger patients. Patients older than aged 70 years demonstrated a higher American Society of Anesthesiologist score (≥ASA III 10.8 vs. 6.6 %, p = 0.008). There was no difference in overall 90-day morbidity (≥70: 45.7 % vs. 7 (95 % CI 1.051-5.798, p = 0.038) and HIPEC duration (95 % CI 1.106-6.235, p = 0.028) were independent factors associated with morbidity in elderly patients.CONCLUSIONS:CRS and HIPEC appear feasible for selected patients older than aged 70 years, albeit with a higher risk of medical complications associated with increased mortality.

The objective of the study was to describe the effect of adjuvant bevacizumab on symptomatic lymphoceles in advanced ovarian cancer after optimal surgery. The effect of bevacizumab on survival was also studied in this cohort. This retrospectivestudy included patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics FIGO 1988 stages IIIB, IIIC, IV) and who had cytoreductive surgery with pelvic and lombo-aortic lymphadenectomy in Gustave Roussy Institute from 2005 to 2014. 255 patients were included. The rate of symptomatic lymphocele was 33.6% (85 out of 253). 61 patients (24.5%) received adjuvant bevacizumab. In multivariate analysis, bevacizumab wasn’t associated with the risk of symptomatic lymphocele wtih hazard ratio at 1.62 (IC95%= 0.87-3.01, p=0.12). The bevacizumab had an impact on disease free survival (DFS) with hazard ratio at 0.6 (IC95%= 0.41-0.91, p=0.01) and the median DFS was 31.7 months in bevacizumab group and 23 months in the control group. In conclusion, bevacizumab wasn’t associated with the risk of symptomatic lymphocele in our study but it had an impact on DFS in patients and prolonged the median DFS by about 9 months in patients with advanced ovarian cancer and complete surgery. Further studies are needed to confirm this result.; L’objectif de cette étude est d’évaluer l’impact du bevacizumab adjuvant sur la lymphocèle symptomatique chez des patientes atteintes d’un cancer de l’ovaire de stade avancé ayant eu une chirurgie complète. L’impact du bevacizumab sur la survie sera ensuite étudié chez ces mêmes patientes. Cette étude rétrospective incluait des patientes atteintes d’un cancer de l’ovaire de stades FIGO (Fédération Internationale de Gynécologie Obstétrique) 1988 IIIB, IIIC et IV ayant été opérées d’une cytoréduction complète avec curages pelviens et lombo-aortique à l’Institut Gustave Roussy entre 2005 et 2014. 255 patientes ont été incluses dans l’étude. Le taux de lymphocèle symptomatique était de 33,6% (85/253). 61 patientes ont été traitées par bevacizumab adjuvant, soit 24,5% des patientes. En analyse multivariée, le traitement par bevacizumab n’était pas significativement associé à la présence d’une lymphocèle symptomatique avec un hazard ratio (HR) à 1,62 (IC95%=0,87-3,01) p=0,12). Le bevacizumab adjuvant avait un impact significatif sur la survie sans récidive avec un HR à 0,6 (IC95%=0,41-0,91 et p=0,01) et la survie médiane sans récidive passait de 23 à 31,7 mois. En conclusion, le bevacizumab n’a pas d’impact sur la survenue de la lymphocèle postopératoire mais a un impact sur la survie sans récidive avec un gain de 8,7 mois dans cette cohorte de patientes de stade avancé et opérées d’une chirurgie complète, ce qui nécessite une confirmation par des essais thérapeutiques.

Background and aims: Complete cytoreduction is the goal of cytoreductive surgery in advanced epithelial ovarian cancer and rectosigmoid resection is a frequent component of this surgery. The aim of this study was to evaluate the morbidity of rectosigmoid resection at the time of cytoreductive surgery and identify risk factors for complications.Methods: We analysed individual data from all patients undergoing rectosigmoid resection as a part of complete cytoreduction between 2005 and 2013. Previously identified risk factors for complications were analysed, so as the use of bevacizumab in adjuvant or neoadjuvant chemotherapy.Results: 69 patients underwent rectosigmoid resection. 32 had primary cytoreductive surgery, 37 interval cytoreductive surgery. 30.4%, (21/69) patients underwent major complications, and it was higher than without rectosigmoid resection (p=0.006). Anastomotic leak rate was 2.89%. Factors associated with major complications were peritoneal stripping of paracolic gutters (p=0.02) and right diaphragmatic coupola (p=0.005), ascites volume 0.02, initial PCI score 0.009). Independent risk factors were menopausal status ORa=13,7 IC 95% [1,2 ; 161.9], intervalsurgery ORa=4,4 IC 95% [1,1 ; 18.8] and peritoneal stripping of the left paracolic gutter ORa=11.3 IC 95% [2.3 ; 54.3]. Use of bevacizumab was not a riskfactor and protective ostomy was not preventive (p=0.71).Conclusions: Morbidity of this surgical procedure is acceptable in order to obtain a complete cytoreduction without residual disease. Protective ileostomy not seems to be a protective factor. Bevacizumab was not associated with higher morbidity; Introduction : Le but de la chirurgie de cytoréduction dans les cancers épithéliaux de l’ovaire est d’obtenir un résidu tumoral nul. La résection recto-sigmoïdienne est un geste réalisé fréquemment dans ce type de chirurgie. Le but de cette étude est d’évaluer la morbidité des résections recto sigmoïdiennes lors de la chirurgie de cytoréduction et d’identifier les facteurs de risque de complications.Matériels et méthodes : Nous avons analysé les données de toutes les patientes ayant eu une résection recto sigmoïdienne lors d’une chirurgie de cytoréduction à l’hôpital européen Georges Pompidou entre 2005 et 2013. Tous les facteurs de risque précédemment identifiés dans la littérature ont été analysés et notamment l’administration de bevacizumab en traitement adjuvant ou néo-adjuvant. Les complications de grade supérieur à 3 dans la classification de Clavien Dindo étaient considérées comme majeures.Résultats : Deux cent vingt-huit patientes ont bénéficié d’une chirurgie de cytoréduction. Pour 116 patientes, il s’agissait d’une chirurgie première et pour 112 d’une chirurgie d’intervalle. 43/228 patientes (18.9%) ont eu des complications majeures et celles-ci étaient plus fréquentes (p=0.04) en cas de chirurgie première (24.1%, 28/11) qu’en cas de chirurgie d’intervalle (13.4%, 15/112). Soixante-neuf patientes ont eu une résection recto sigmoïdienne, 32 dans le cadre d’une chirurgie première. La morbidité était plus importante en cas de résection sigmoïdienne 30.4%, (21/69) qu’en cas de chirurgie sans résection (14.6%, 22/151) (p=0.006). Le taux de lâchage de l’anastomose était de 2.89%. En analyse uni variée, nous avons identifié comme facteurs de risque de complications ; la réalisation de résections péritonéales (coupolediaphragmatique droite (p=0.005), gouttières pariéto-coliques droite (p=0.03) gauche (p=0.02)), le volume initial d’ascite(p=0.02) et le Peritoneal Carcinomatosis Index initial (p=0.009). Les facteurs de risque indépendants de morbidité étaientla ménopause, ORa=13,7 IC 95% [1,2 ; 161.9], la chirurgie après chimiothérapie néo-adjuvante ORa=4,4 IC 95% [1,1 ; 18.8]et la réalisation d’un stripping péritonéal au niveau de la gouttière pariéto-colique gauche ORa=11.3 IC 95% [2.3 ; 54.3].L’administration de bevacizumab n’était pas associée à une augmentation de la morbidité et l’iléostomie ne semble pas être un facteur protecteur (p=0.71).Conclusion : Dans notre étude, la morbidité de ce geste chirurgical est acceptable dans le but d’obtenir un résidu tumoralnul. L’iléostomie n‘est pas être un facteur protecteur contre les complications majeures et l’administration debevacizumab n’augmente pas le taux de complications.